一个国际研究团队在近日出版的《科学》杂志上宣称，由于胰腺癌的肿瘤大部分与血管无关，针对胰腺癌症的传统药物比如美国礼来公司的健择（Gemza）很难接近肿瘤并杀死肿瘤细胞，导致这些药物失效。
英国癌症研究所剑桥研究院的大卫·图文森领导了该项研究。研究人员让经过基因改造的老鼠患上胰腺癌，他们发现，老鼠体内只有很少的肿瘤与血管，人类也同样如此。这表明，胰腺癌可能同其他癌症不同，不需要给肿瘤供应丰富的血液，所以，通过限制血液供应以杀死肿瘤的血管内皮生长因子（VEGF）抑制剂对胰腺癌肿瘤不起作用。
研究人员同时发现，在老鼠和胰腺癌症病人身上进行的研究表明，将Gemza同美国无限制药公司的药物IPI-926结合，可能更好地战胜胰腺癌。不过，还需要进行进一步的安全测试。
全世界每年有23万人被诊断出患上胰腺癌，只有3%的人能活过5年。而且，胰腺癌扩散很快，当很多人被诊断出身患该癌症时，已无力回天。（生物谷Bioon.com）
生物谷推荐原始出处：
Science May 21, 2009 DOI: 10.1126/science.1171362
Inhibition of Hedgehog Signaling Enhances Delivery of Chemotherapy in a Mouse Model of Pancreatic Cancer
Kenneth P. Olive 1, Michael A. Jacobetz 1, Christian J. Davidson 2, Aarthi Gopinathan 3, Dominick McIntyre 1, Davina Honess 1, Basetti Madhu 1, Mae A. Goldgraben 1, Meredith E. Caldwell 1, David Allard 1, Kristopher K. Frese 1, Gina DeNicola 3, Christine Feig 1, Chelsea Combs 2, Stephen P. Winter 1, Heather Ireland 1, Stefanie Reichelt 1, William J. Howat 1, Alex Chang 4, Mousumi Dhara 4, Lifu Wang 5, Felix Rückert 6, Robert Grützmann 6, Christian Pilarsky 6, Kamel Izeradjene 7, Sunil R. Hingorani 7, Pearl Huang 8, Susan E. Davies 9, William Plunkett 10, Merrill Egorin 11, Ralph H. Hruban 4, Nigel Whitebread 12, Karen McGovern 12, Julian Adams 12, Christine Iacobuzio-Donahue 4, John Griffiths 1, David A. Tuveson 1*
1 Cancer Research UK, Cambridge Research Institute, The Li Ka Shing Centre, Robinson Way, Cambridge, CB2 ORE, UK.
2 Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA 19104, USA.
3 Cancer Research UK, Cambridge Research Institute, The Li Ka Shing Centre, Robinson Way, Cambridge, CB2 ORE, UK.; Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA 19104, USA.
4 Departments of Oncology and Pathology, The Sol Goldman Pancreatic Cancer Research Center, Sidney Cancer Center and Johns Hopkins University, Baltimore, MD 21287, USA.
5 Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA 19104, USA.; Department of Gastroenterology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China.
6 Department of Surgery, University Hospital Dresden, Fetscherstr. 74, 01307 Dresden, Germany.
7 Clinical Research and Public Health Sciences Division, Fred Hutchinson Cancer Research Center, and University of Washington, Seattle, WA 98109, USA.
8 Oncology Franchise, Merck and Co, North Wales, PA 19454, USA.
9 Department of Histopathology, Addenbrooke’s Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, CB2 2QQ, UK.
10 Univ. of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
11 Division of Hematology and Oncology, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA.
12 Infinity Pharmaceuticals Inc, Cambridge, MA 01239, USA.
Pancreatic ductal adenocarcinoma (PDA) is among the most lethal human cancers, in part because it is insensitive to many chemotherapeutic drugs. Studying a mouse model of PDA that is refractory to the clinically used drug gemcitabine, we found that the tumors in this model were poorly perfused and poorly vascularized, properties that are shared with human PDA. We tested whether the delivery and efficacy of gemcitabine in the mice could be improved by coadministration of IPI-926, a drug that depletes tumor-associated stromal tissue by inhibiting the Hedgehog cellular signaling pathway. The combination therapy produced a transient increase in intratumoral vascular density and intratumoral concentration of gemcitabine, leading to transient stabilization of disease. Thus, inefficient drug delivery may be an important contributor to chemoresistance in pancreatic cancer.
